Biocides are chemical substances that are capable of killing or controlling various living organisms. Biocides have a variety of uses in modern society, for example, as disinfectants, in pest control, in food for feedstock or food handling and preparation, as preservatives for wood and other materials, and in water systems. The Biocidal Products Directive 98/8/EC (BPD), classifies biocides into 23 different product types (i.e. application categories). Biocides are frequently added to other materials, notably liquids, so as to provide protection of that material from unwanted microorganisms.
The development of new and useful biocides requires consideration of many elements such as the following: the type(s) of organism whose control is desired; the manner in which the biocide is to be deployed; the costs of preparing and delivering the biocide; environmental or disposal issues; and so on. Depending on the potential use(s) envisioned, primary considerations are likely to include both its potency against the organisms targeted, as well as its biocompatibility, e.g. lack of toxicity against the humans or animals which may come into contact with it. Biocides may have a broad or narrow spectrum of activity. Biocides may be inorganic or organic depending on their intended use.
Many of the organic biocides in current use in the pharmaceutical field are based on molecules having a relatively limited variety of functional groups, including groups such as quaternary ammoniums, biguanides, primary, secondary or tertiary amines, amine-N-oxides and amides. These functional groups impart varying degrees of hydrophilicity to the molecules in which they are incorporated. In addition to these functional groups, broad spectrum biocides may require hydrophobic elements in order to penetrate biological membranes and achieve their full potency. Hydrophobicity in biocides can be achieved through incorporation of long chain hydrocarbons into the structure of the molecule. It is known that long chain hydrocarbons, when included into the structure of molecules containing biocidal groups, can improve the activity of the biocide. Thus, many organic biocides have both a lipophilic and hydrophilic component. Discovery of biocides that provide a desired balance between lipophilicity and hydrophilicity of a biocide for its field of use is a desirable result, and this balance can depend on the nature of the composition in which the biocide resides as well as the circumstances of its use. In the case of compositions intended for use in and around the eyes and for treating contact lens, such a balance can be highly challenging due in part to the extreme sensitivity of the eye to potential sources of irritation.
Although necessary for the effectiveness of the organic biocide, hydrophobicity can also cause damage to mammalian cells. Certain biocides used in conjunction with contact lens care and/or disinfection, in particular biocidal groups with long chain hydrocarbons, are known to cause a number of problems, including, for example, adsorption onto the surfaces of contact lenses or lens cases, which may lead to irritation to the wearer as a result of such adsorption, and loss of biocide available for disinfection. Conversely, biocides that are excessively hydrophilic tend to have diminished antimicrobial activity.
U.S. Pat. No. 3,931,319 (Jan. 6, 1976), U.S. Pat. No. 4,001,432 (Jan. 4, 1977) and U.S. Pat. No. 4,012,446 (Mar. 15, 1977), all issued to Green, et al., disclose a group of high molecular weight “capped” linear polymeric quaternary ammonium compounds found to be effective microbiocides (antimicrobials). The Green, et al. compounds are “capped” in the sense that both ends of the chains terminate in quaternary ammonium moieties. In a continuation-in-part application, now U.S. Pat. No. 4,027,020 (May 31, 1977), Green, et al. disclose a process for making randomly capped linear polymeric quaternary ammonium compounds; that is, the polymers produced by the improved process include those with very short chain lengths as well as those having relatively long chain lengths. These compounds were also found to have antimicrobial activity.
U.S. Pat. No. 4,407,791 (Oct. 4, 1983) and U.S. Pat. No. 4,525,346 (Jun. 25, 1985), both issued to Stark, disclose disinfecting solutions for contact lenses, wherein the aqueous solutions contain the Green, et al. polymers, including the compound commercially known as Onamer M® or PolyQuad®.
U.S. Pat. No. 4,110,263 (Lindemann et al.) describes mild cleansing compositions containing alkyleneoxylated bisquaternary ammonium compounds.
WIPO Publication No. 96/06603 (Park et al.) describes polyalkyene oxide containing quaternary ammonium antimicrobial agents.
U.S. Pat. No. 5,145,643 (Dziabo et al.) describes nonoxidative ophthalmic compositions and methods for preserving and using same.
The existing art notwithstanding, there still exists a need for biocides with one or any combination of the following: an effective balance of hydrophobic and hydrophilic elements; useful antimicrobial activity; non-irritating; low toxicity; compatibility with the materials and tissue with which they come into contact. The present invention is directed to achieving these and other aims.